{"doi":"10.1038/s41598-020-75615-3","title":"Impaired mitochondrial medium-chain fatty acid oxidation drives periportal macrovesicular steatosis in sirtuin-5 knockout mice","abstract":"Abstract Medium-chain triglycerides (MCT), containing C 8 –C 12 fatty acids, are used to treat several pediatric disorders and are widely consumed as a nutritional supplement. Here, we investigated the role of the sirtuin deacylase Sirt5 in MCT metabolism by feeding Sirt5 knockout mice (Sirt5KO) high-fat diets containing either C 8 /C 10 fatty acids or coconut oil, which is rich in C 12 , for five weeks. Coconut oil, but not C 8 /C 10 feeding, induced periportal macrovesicular steatosis in Sirt5KO mice. 14 C–C 12 degradation was significantly reduced in Sirt5KO liver. This decrease was localized to the mitochondrial β-oxidation pathway, as Sirt5KO mice exhibited no change in peroxisomal C 12 β-oxidation. Endoplasmic reticulum ω-oxidation, a minor fatty acid degradation pathway known to be stimulated by C 12 accumulation, was increased in Sirt5KO liver. Mice lacking another mitochondrial C 12 oxidation enzyme, long-chain acyl-CoA dehydrogenase (LCAD), also developed periportal macrovesicular steatosis when fed coconut oil, confirming that defective mitochondrial C 12 oxidation is sufficient to induce the steatosis phenotype. Sirt5KO liver exhibited normal LCAD activity but reduced mitochondrial acyl-CoA synthetase activity with C 12 . These studies reveal a role for Sirt5 in regulating the hepatic response to MCT and may shed light into the pathogenesis of periportal steatosis, a hallmark of human pediatric non-alcoholic fatty liver disease.","journal":"Scientific Reports","year":2020,"id":91564,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":45,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":458698,"name":"Sivakama S. Bharathi","orcid":"0000-0003-0611-2778","position":1,"is_corresponding":false},{"id":458699,"name":"Yuxun Zhang","orcid":"0000-0002-6682-012X","position":2,"is_corresponding":false},{"id":458700,"name":"Xuejun Zhao","orcid":"0000-0001-5715-8800","position":3,"is_corresponding":false},{"id":458663,"name":"Steven F. Dobrowolski","orcid":"0000-0001-5810-4863","position":4,"is_corresponding":false},{"id":458701,"name":"Kevin Peasley","orcid":"0000-0002-3409-9008","position":5,"is_corresponding":false},{"id":428724,"name":"Sunder Sims‐Lucas","orcid":"0000-0003-1908-4809","position":6,"is_corresponding":false},{"id":277667,"name":"Satdarshan P. Monga","orcid":"0000-0002-8437-3378","position":7,"is_corresponding":false},{"id":458697,"name":"Eric S. Goetzman","orcid":"0000-0001-9476-309X","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T22:29:21.932251Z","pmid":"33110171","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}